Preparation method of a colloidal system of stabilisation and controlled release of royal jelly components for various uses

Abstract

Preparation method of a colloidal system of stabilisation and controlled release of royal jelly ingredients, wherein the said system is characterized by the extraction of the components of the royal jelly and the simultaneous encapsulation in combinatorial liposome—cyclodextrin carriers for achieving controlled release, taking advantage of the special features of both carriers, namely: the ability of cyclodextrins to encapsulate polyphenols and their enhanced skin penetration ability as well as the ability of liposomes in encapsulating large amounts of components of various degrees of polarity, for local component transport and for controlled release rate.

The invention claimed is: 
     
         1 . A preparation method of a colloidal stabilization system and controlled release of royal jelly components, comprising:
 in a first stage fresh royal jelly is kept in a temperature of 5-7° C. and contains 10-hydroxydecenoic acid in a concentration of >1.8% w/w and is then allowed to reach room temperature;   in a second stage the fresh royal jelly is gradually dissolved, under stirring in a system of solvents which consists of deionized water, in which hydroxypropyl-β-cyclodextrin or β-cyclodextrin or γ-cyclodextrin in a concentration of 1%-22% w/w has been pre-dissolved and either vegetable 1,3-propanediol or glycerol or vegetable butylene glycol in a ratio of vegetable 1,3-propanediol or glycerol or vegetable butylene glycol to water of from 5/95 to 90/10, where the concentration of royal jelly in the solvent system ranges between 0.5% to 6.0% w/w;   in a third stage the system of royal jelly/cyclodextrin/solvent system is subjected to stirring at 1000 to 3000 rpm for 30 to 90 minutes at a temperature of 20° C. to 26° C.;   in a fourth stage, the system royal jelly/cyclodextrin/solvent is added to a liposomal system at a rate of 10 ml/sec at a concentration of 1.0-7.5% w/w, after complete addition of which a pH of the system is set in a range 5.0-8.2 and either Disodium Ethylenediaminetetraacetic acid or Tetrasodium Glutamate Diacetate is added at a concentration of 0.1-0.2% w/w the system subjected to stirring at 4000 rpm for 4 hours, to form a mixture;   in a fifth stage, the mixture is kept in a hermetically sealed container to rest for 24 hours at 5-7° C. and then, the colloidal system is cold filtered through an array of cartridge filters of pore size 5 μm-1 μm-0.45 μm and the pH is retested, and the pH is readjusted to be in the range of 5.0-8.2 if the pH outside the range of 5.0-8.2;   in a sixth stage, the system is allowed to reach room temperature and a mean hydrodynamic particles diameter is measured which should range between 220 nm to 650 nm with a polydispersity index ranging from 0.25 to 0.68, wherein if the measured mean hydrodynamic particles diameter or polydispersity index values are out of these ranges, the colloidal system is filtered through an array of cartridge filters with pore size 0.45 μm-0.2 μm at room temperature; and   in a final stage, after finding that the mean hydrodynamic diameter is between 220 nm to 650 nm and the polydispersity index is from 0.25 to 0.68, a total content of polyphenols and total content of 10-hydroxydecenoate acid are measured, while continuously a release rate of polyphenols and 10-hydroxydecenoic acid is measured in a buffer at pH 7.2 at 37° C. and the colloidal system is stored in a dark container at a temperature of 5-7° C., and is stable for 1 year.   
     
     
         2 . A preparation method of a colloidal stabilization system and controlled release of royal jelly ingredients according to  claim 1  wherein the deionized water quality is: ≤1 μS/cm at 25° C. 
     
     
         3 . A preparation method of a colloidal stabilization system and controlled release of royal jelly ingredients according to  claim 1 , wherein the deionized water is produced by introducing water of a water supply network into a tank with a pumping unit, passing the water through an automatic turbidity and activated carbon filter, and then a scale inhibitor is dosed to remove water hardness, and then the water enters a main unit of a reverse osmosis unit, of 350 lt/h capacity with 70% recovery after having passed first, through a 1 micron cartridge filter and the water is then tanked in a stainless steel tank, from which the water supplies a deionizer. 
     
     
         4 . A preparation method of a colloidal stabilization system and controlled release of royal jelly ingredients according to  claim 1 , wherein the liposomal system, which consists of 50%-95% Phosphatidylcholine, 2%-10% Phosphatidylethanolamine, 0%-3% Lysophosphatidylcholine, 0%-3% Phosphatidylinositol, 0%-3% Phosphatidate acid, 0%-22% cholesterol, 0-17% bile salts, is performed, in solvent 1.3-propanediol or glycerol, in a concentration ranging from 20/80 to 80/20% w/w, is produced in a container. 
     
     
         5 . A preparation method of a colloidal stabilization system and controlled release of royal jelly ingredients according to  claim 1 , wherein the total content of polyphenols in the system is greater than 200 mg/L GAE. 
     
     
         6 . A preparation method of colloidal stabilization system and controlled release of royal jelly ingredients according to  claim 1 , wherein the total content of 10-hydroxydecenoic acid in the system is greater than 0.04% w/w. 
     
     
         7 . A preparation method of colloidal stabilization system and controlled release of royal jelly ingredients according to  claim 1 , wherein a cumulative release of polyphenols at pH 7.2 and temperature 37° C. is 25-75% in 8 hours with total release of encapsulated polyphenols from the system at 24 hours. 
     
     
         8 . A preparation method of colloidal stabilization system and controlled release of royal jelly ingredients according to  claim 1 , wherein a cumulative release of 10-hydroxydecenoate acid at pH 7.2 and 37° C. is 40%-80% in 8 hours with total release of encapsulated 10-hydroxydecenoic acid from the system in 12 hours. 
     
     
         9 . A stable colloidal dispersion system of royal jelly that releases in a controlled manner its components which is produced according to the method of  claim 1 , wherein its total content of polyphenols is greater than 200 mg/L GAE, its total content of 10-hydroxydecenoic acid is greater than 0.04% w/w, wherein a cumulative release of polyphenols at pH 7.2 and temperature 37° C. ranges from 25% to 75% in 8 hours with total release taking place in 24 hours, and wherein a cumulative release of 10-hydroxydecenoic acid is 40% up to 80% in 8 hours with total release taking place in 12 hours.